Endometriosis is an estrogen-dependent gynecologic disorder, defined as the presence of endometrial-like tissue outside the uterine cavity, which affects 6% to 10% women of reproductive age from all ethnic and social groups. The degree of endometriosis is staged according to the classification system of the American Society of Reproductive Medicine (Fertil. Steril., 67:81721 (1997)) into minimal, mild, moderate, and severe disease. At present, the gold standard for diagnosis of endometriosis is laparoscopic inspection with histologic confirmation after retrieval of lesions.
As endometriosis can be progressive in up to 50% of women, early noninvasive diagnosis has the potential to offer early treatment and prevent progression. A noninvasive test for endometriosis would be also useful for women with pelvic pain and/or subfertility with normal ultrasound results. The goal of a non-invasive test is that no women with endometriosis or other significant pelvic pathology are missed who might benefit from medical therapy or surgery. There are reports of biomarkers that maybe useful for early or noninvasive detection. For example, Fossbinder et al. (Fertil. Steril., 99:1135-1145 (2013)) point out that cancer antigen 125 (CA-125) is the most used peripheral biomarker of endometriosis, and that out of 28 biomarkers, multivariate analysis of plasma samples, showed that annexin V, vascular endothelial growth factor (VEGF), CA-125, and soluble intercellular adhesion molecule-1 (sICAM-1)/or glycodelinin enabled the diagnosis of endometriosis in women who had disease undetected by ultrasound. Surprisingly, inflammatory molecules did not emerge as biomarkers in a panel with the best diagnostic performers.
May et al. (Hum. Reprod. Update, 17:637-53 (2011)) conducted a systematic review of published results that assessed over 200 potential biomarkers for endometriosis, including hormones and their receptors, cytokines, and factors identified using proteomics, and analyzed histological results from endometrial tissue. Some of those putative biomarkers related to nerve fiber growth or cell cycle control, while others were cytokines including IL-1β, IL-IR type II, IL-6, IL-8, IL-13, IL-15, tumor necrosis factor (TNF)-α, (MCP-1); macrophage-stimulating protein (RANTES); steroids and hormones, e.g., aromatase and hydroxysteroid dehydrogenase enzymes; growth factors; e.g., TGFβ family, insulin-like growth (IGF) factors, hepatocyte growth factor (HGF) and its receptor, annexin-1; cell adhesion and extracellular matrix molecules, e.g., the r33 integrin subunit α3β1 integrin, αvβ5 and αvβ5 integrins, E-cadherin; extracellular matrix molecules (ECM), e.g., ICAM-1, focal adhesion kinase (FAK); tissue remodeling molecules, e.g., matrix metalloproteinase (MMP) family, tissue inhibitors of metalloproteinases (TIMPs), urokinase; angiogenesis, e.g., vascular endothelial growth factor (VEGF), angiopoeitin-1 and -2 molecules; associated with apoptosis and cell cycle control, e.g., calpain 5, MCL-1, Bak, Ki67, telomerase activity, proliferating cell nuclear antigen, Pak-1, phosphorylated ERK I 12, c-myc, survivin; reactive oxygen and nitrogen species, e.g., endothelial xanthine oxidase, WT-1, CCL16, CCL21, HOXA10 and COX-2.